TNF and Sepsis: At the molecular level, sepsis triggers TLR4/NF-κB and NLRP3 inflammasome activation in alveolar macrophages, driving a cytokine storm characterized by TNF-α and IL-1β-mediated upregulation of endothelial adhesion molecules (ICAM-1/VCAM-1) and IL-6-induced JAK-STAT3 signaling, which collectively exacerbate vascular permeability (1, 6).